The invention relates to thrombin-containing compositions and more broadly to the stability of such compositions. The thrombin-containing compositions can be used for hemostasis applications.
Thrombin can be used in hemostasis applications to catalyze coagulation-related reactions. For example, thrombin can be used to catalyze the formation of fibrin which can aide in clotting formation in wounds. Collagen-thrombin compositions or their use in hemostasis applications can be found, for example, in U.S. Pat. Nos. 4,515,637, 4,696,812, 4,965,203, 5,130,244, 5,290,552, 5,997,811, 6,096,309, 7,473,543, 8,071,090, United States Patent Application Publication No. 2006/0088518, and European Patent Nos. EP0277096A2, EP1221479B, EP1927658A1, and EP0505604A1.
One exemplary commercial product which utilizes such a composition is Vitagel®, which includes thrombin, microfibrillar collagen, sodium chloride (NaCl), PEG 1000 and calcium chloride (CaCl2), and is being marketed for hemostasis applications. While the stability of VITAGEL® is established, typical formulations require the product to be manufactured with high initial thrombin activity levels (e.g., about 800 IU/ml) in order to maintain an effective thrombin activity level (e.g., at least 300 IU/ml) over the entire shelf-life of the product. The addition of excess thrombin contributes to high manufacturing costs.
There remains a need for improved stability in compositions containing thrombin and collagen and methods for making the same.